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Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action

TitleYeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action
Publication TypeJournal Article
Year of Publication2004
AuthorsBaetz, K, McHardy, L, Gable, K, Tarling, T, Reberioux, D, Bryan, J, Andersen, RJ, Dunn, T, Hieter, P, Roberge, M
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Pagination4525-4530
Date PublishedMar
Type of ArticleArticle
ISBN Number0027-8424
KeywordsDELETION, GENE, INVASION, MUTANT, PATHWAYS, PDK1, SACCHAROMYCES-CEREVISIAE, SUPPRESSORS
Abstract

Methods to systematically test drugs against all possible proteins in a cell are needed to identify the targets underlying their therapeutic action and unwanted effects. Here, we show that a genome-wide drug-induced haploinsufficiency screen by using yeast can reveal drug mode of action in yeast and can be used to predict drug mode of action in human cells. We demonstrate that dihydromotuporamine C, a compound in preclinical development that inhibits angiogenesis and metastasis by an unknown mechanism, targets sphingolipid metabolism. The systematic, unbiased and genome-wide nature of this technique makes it attractive as a general approach to identify cellular pathways affected by drugs.

URL<Go to ISI>://000220648700037